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Breast Facts & Figures 2019-2020 Contents Cancer Basic Facts 1 Risk Factors 12 Figure 1. Distribution of Female Breast Cancer Subtypes, Table 4. Factors That Increase the Relative Risk for Invasive Breast US, 2012-2016 2 Cancer in Women 13

Breast Cancer Occurrence 3 Breast Cancer 20 Table 1. Estimated New DCIS and Invasive Breast Cancer Table 5. (%), Women 45 and Older, Cases and Deaths among Women by Age, US, 2019 3 US, 2018 21 Table 2. Age-specific Ten-year Probability of Breast Cancer Table 6. Mammography (%) by State, Women 45 Diagnosis or Death for US Women 4 and Older, 2016 22 Figure 2. Age-specific Female Breast Cancer Rates by Race/Ethnicity, US, 2012-2016 4 Breast Cancer Treatment 23 Figure 3. Female Breast Cancer Incidence (2012-2016) Figure 12. Female Breast Cancer Treatment Patterns (%), and Death (2013-2017) Rates by Race/Ethnicity, US 5 by Stage, US, 2016 24 Figure 4. Distribution of Breast Cancer Subtypes by What Is the American Cancer Society Doing Race/Ethnicity, Ages 20 and Older, US, 2012-2016 5 about Breast Cancer? 26 Figure 5. Female Breast Cancer Stage Distribution by Race/Ethnicity, Ages 20 and Older, US, 2012-2016 6 Sources of Statistics 30

Figure 6. Trends in Incidence Rates of Ductal References 32 In Situ and Invasive Female Breast Cancer by Age, US, 1975-2016 7 Figure 7. Trends in Female Breast Cancer Incidence Rates by Race/Ethnicity, US, 2001-2016 8 Figure 8. Trends in Female Breast Cancer Death Rates by Race/Ethnicity, US, 1975-2017 8 Table 3. Female Breast Cancer Incidence and Death Rates by Race/Ethnicity and State 9 Figure 9. Geographic Variation in Female Breast Cancer Death Rates by Race/Ethnicity, 2013-2017 10 Figure 10. Trends in Female Breast Cancer 5-year Relative Survival Rates by Race, US, 1975-2015 11 Figure 11. Five-year Breast Cancer-specific Survival Rates (%) by Stage at Diagnosis and Race/Ethnicity, US, 2009-2015 11

This publication attempts to summarize current scientific information Global Headquarters: American Cancer Society Inc. about breast cancer. Except when specified, it does not represent 250 Williams Street, NW, , GA 30303-1002 404-320-3333 the official policy of the American Cancer Society. ©2019, American Cancer Society, Inc. All rights reserved, including the right to reproduce this publication or portions thereof in any form. Suggested citation: American Cancer Society. Breast Cancer Facts & For permission, email the American Cancer Society Legal Figures 2019-2020. Atlanta: American Cancer Society, Inc. 2019. Department at [email protected]. Breast Cancer Basic Facts

What is breast cancer? How is breast cancer staged? Breast cancer is a group of in which cells in The extent of the cancer and its spread at the time of breast tissue change and divide uncontrolled, typically diagnosis determines its stage, which is essential for resulting in a lump or mass. Most breast begin in guiding treatment options and prognosis (prediction of the lobules (milk glands) or in the ducts that connect the outcome). The two main staging systems for lobules to the . cancer are the American Joint Committee on Cancer (AJCC) staging system, typically used in clinical settings, and the Surveillance, , and End Results What are the of (SEER) summary staging system, used for descriptive and breast cancer? statistical analysis of tumor registry data. The AJCC Breast cancer typically has no symptoms when the tumor system was recently updated (effective January 2018) to is small and most easily treated, which is why screening add prognostic stage groups.1 AJCC anatomic stage is is important for early detection. The most common based on extent of the cancer (in the breast, regional physical sign is a painless lump. Sometimes breast cancer lymph nodes, and distant spread), while prognostic stage spreads to underarm lymph nodes and causes a lump or also includes information on the presence of swelling, even before the original breast tumor is large receptors (ER), receptors (PR), levels of enough to be felt. Less common signs and symptoms human epidermal 2 (HER2, a include breast or heaviness; persistent changes, such growth-promoting protein) and/or extra copies of the as swelling, thickening, or redness of the ; and nipple HER2 gene (HER2+/HER2-), and grade (reflecting how changes, such as spontaneous discharge (especially if closely the cancer’s microscopic appearance looks like bloody), scaliness, or retraction. Any persistent change in normal breast tissue). In this document, we generally the breast should be evaluated by a physician. refer to the SEER summary stage except in the section on the description of breast cancer treatment (page 23), which references AJCC anatomic stage. How is breast cancer diagnosed? Breast cancer is typically detected either during According to the SEER summary stage system: screening, before symptoms have developed, or after a • In situ stage refers to the presence of abnormal notices a lump. Most masses seen on a cells that are confined to the layer of cells where mammogram and most breast lumps turn out to be they originated. benign (not cancerous). When cancer is suspected, tissue for microscopic analysis is usually obtained from a • Local stage refers to invasive cancer that is confined needle (fine-needle or larger core-needle) and less to the breast. often from a surgical biopsy. Selection of the type of • Regional stage refers to cancer that has spread to biopsy is based on multiple factors, including the size and surrounding tissue and/or nearby lymph nodes. location of the mass, as well as patient factors and preferences and resources. • Distant stage refers to cancer that has spread to distant organs and/or lymph nodes, including nodes above the collarbone.

Breast Cancer Facts & Figures 2019-2020 1

What are the types of breast cancer? Figure 1. Distribution of Female Breast Cancer Subtypes, US, 2012-2016 In Situ HR-/HER2+ 4% Historically, ductal (DCIS) and in situ (LCIS), also known as lobular neoplasia, HR-/HER2- were considered the two main types of in situ breast cancer. 12% However, LCIS is generally believed to be a benign condition associated with increased breast cancer risk, but without HR+/HER2+ 11% the potential to progress to invasive cancer, so it was removed from the latest edition of the AJCC breast cancer 2 HR+/HER2- staging system. DCIS, on the other hand, is a precursor 73% to invasive cancer, although not all DCIS progresses. In fact, DCIS sometimes grows so slowly that even without treatment it would not affect a woman’s health. Long-term studies have found that only 20%-53% of women with HR = receptor, HER2 = human receptor 2. untreated DCIS are ultimately diagnosed with invasive Source: North American Association of Central Cancer Registries (NAACCR), 2019. breast cancer.3-5 DCIS patients who are premenopausal at ©2019, American Cancer Society, Inc., Surveillance diagnosis or who had their DCIS detected by palpation are at greater risk of being diagnosed with a future invasive carcinoma, representing about 15% of invasive breast 6, 7 breast cancer. During 2012-2016, DCIS represented 16% cancers.8 Tubular, mucinous, cribriform, and papillary 8 of all breast cancer diagnoses. carcinoma are rare breast cancer subtypes that are generally associated with favorable prognoses.9 See page 13 for additional information on DCIS and LCIS. Inflammatory breast cancer is an uncommon but Cancer Facts & More information can also be found in the aggressive type of breast cancer that is characterized by Figures 2015, Special Section: Breast Carcinoma In Situ . swelling and redness of the skin of the breast.

Invasive Molecular subtypes Most (81%) breast cancers are invasive, or infiltrating, Breast cancer molecular subtypes are determined which means the abnormal cells have broken through the through gene expression analysis, a costly and walls of the glands or ducts where they originated and complicated process that is not currently standard grown into surrounding breast tissue. Although breast clinical practice. However, these subtypes can be cancer was historically referred to as a single disease, approximated using routine methods for clinical it is now considered a group of diseases, consisting of evaluation of biological markers (ER, PR, HER2, and four major molecular subtypes and at least 21 distinct sometimes others). Hormone receptor positive (HR+) histological subtypes (type of tissue in which the cancer cancers are those that test positive for ER or PR, or both. originates) that differ in risk factors, presentation, Information about grade and proliferation (rate of cell response to treatment, and outcomes. division) is also sometimes used to assign subtype.

Histologic subtypes The four main molecular subtypes are described below. is based on the size, shape, and arrangement of It is worth noting that there are overlaps between breast cancer cells. More than 75% of invasive breast categories and the clinical approximations do not cancers are now histologically categorized as “no special perfectly correspond to the molecular breast cancer type,” historically called “ductal” .8 The most subtypes as described on the next page.10 common special histologic subtype is invasive lobular

2 Breast Cancer Facts & Figures 2019-2020 Luminal A (HR+/HER2-): This is the most common type majority (about 75%) of triple negative breast cancers fall of breast cancer (Figure 1) and tends to be slower-growing in to the basal-like subtype defined by gene expression and less aggressive than other subtypes. Luminal A profiling.13 Triple negative breast cancers have a poorer tumors are associated with the most favorable prognosis prognosis than other subtypes, in part because treatment in part because they are usually responsive to hormonal advances have lagged behind other molecular subtypes. 14, 15 therapy (see page 26).11, 12 These cancers occur at twice the rate in black women compared to white women in the US, and are also more Luminal B (HR+/HER2+): In addition to being HR+, this common in premenopausal women and those with a subtype was originally characterized clinically as always BRCA1 gene .16 being positive for HER2, but more recently has been defined by being highly positive for the protein Ki67 (an indicator HER2-enriched (HR-/HER2+): In the past, this subtype of a large number of actively dividing cells) and/or HER2. had the worst prognosis; however, the widespread use of Luminal B breast cancers tend to be higher grade than targeted therapies for HER2+ cancers has substantially luminal A and thus are associated with poorer outcomes.11, 12 improved outcomes for these patients.14, 17 For more information about the treatment of HER2+ breast cancers, Basal-like (HR-/HER2-): These cancers are also called see the section on on page 26. triple negative because they are ER-, PR- and HER2-. The

Breast Cancer Occurrence

How many cases and deaths are How many women alive today have expected to occur in 2019? ever had breast cancer? In 2019, an estimated 268,600 new cases of invasive More than 3.8 million US women with a history of breast breast cancer will be diagnosed among women (Table 1) cancer were alive on January 1, 2019.18 Some of these and approximately 2,670 cases will be diagnosed in men. women were cancer-free, while others still had evidence In addition, an estimated 48,100 cases of DCIS will be of cancer and may have been undergoing treatment. diagnosed among women. Approximately 41,760 women More than 150,000 breast cancer survivors are living and 500 men are expected to die from breast cancer in 2019. with metastatic disease, three-fourths of whom were originally diagnosed with stage I-III.19

Table 1. Estimated New DCIS and Invasive Breast Cancer Cases and Deaths among Women by Age, US, 2019 What is the risk of being diagnosed DCIS cases Invasive cases Deaths with breast cancer? Age Number % Number % Number % <40 1,180 2% 11,870 4% 1,070 3% Approximately 1 in 8 women (13%) will be diagnosed 40-49 8,130 17% 37,150 14% 3,250 8% with invasive breast cancer in their lifetime and 1 in 39 50-59 12,730 26% 61,560 23% 7,460 18% women (3%) will die from breast cancer (Table 2).20 60-69 14,460 30% 74,820 28% 9,920 24% Lifetime risk is an average of risk for all women and 70-79 8,770 18% 52,810 20% 8,910 21% accounts for deaths from other causes that may preempt 80+ 2,830 6% 30,390 11% 11,150 27% All ages 48,100 268,600 41,760 a breast cancer diagnosis.

Estimates are rounded to the nearest 10. Percentages may not sum to 100 due to rounding. Breast cancer risk varies by age and race/ethnicity: ©2019, American Cancer Society, Inc., Surveillance Research

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Table 2. Age-specific Ten-year Probability of Breast Figure 2. Age-specific Female Breast Cancer Incidence Cancer Diagnosis or Death for US Women Rates by Race/Ethnicity, US, 2012-2016 Diagnosed with Dying from 500 Current age invasive breast cancer breast cancer Non-Hispanic White 20 0.1% (1 in 1,479) <0.1% (1 in 18,503) Non-Hispanic Black American Indian/Alaska Native 30 0.5% (1 in 209) <0.1% (1 in 2,016) Hispanic 40 1.5% (1 in 65) 0.2% (1 in 645) Asian/Pacific Islander 50 2.4% (1 in 42) 0.3% (1 in 310) 400 60 3.5% (1 in 28) 0.5% (1 in 193) 70 4.1% (1 in 25) 0.8% (1 in 132) 80 3.0% (1 in 33) 1.0% (1 in 101) Lifetime risk 12.8% (1 in 8) 2.6% (1 in 39) 300 Note: Probability is among those who have not been previously diagnosed with cancer. Percentages and “1 in” numbers may not be numerically equivalent due to rounding.

©2019, American Cancer Society, Inc., Surveillance Research 100,000 per Rate 200

Age • Breast cancer incidence and death rates increase 100 with age until the seventh decade (Figure 2). The decrease in incidence rates that occurs in women 80 years of age and older may reflect lower rates of 0 20-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85 screening, the detection of cancers by mammography Age

before 80 years of age, and/or incomplete detection. Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. • During 2012-2016, the median age at the time of Source: NAACCR, 2019. Data for American Indians/Alaska Natives are based on Purchased/Referred Care Delivery Area (PRCDA) counties. 20 breast cancer diagnosis was 62. This means that ©2019, American Cancer Society, Inc., Surveillance Research half of women who developed breast cancer were 62 years of age or younger at the time of diagnosis. The median age of diagnosis was slightly younger for • NH black women have higher incidence rates than black women (60) than white women (63).20 NH whites before age 40 (Figure 2) and are more likely to die from breast cancer at every age. • Table 2 provides 10-year probabilities of invasive breast cancer diagnosis or death for women of • The distributions of breast cancer subtypes for the different ages. By 10-year age groups, the probability major racial/ethnic groups are shown in Figure 4. of a breast cancer diagnosis is highest for women in HR+/HER2- breast cancers are by far the most their 70s (4.1%), while breast cancer death is most common subtype among women of all races/ likely among women in their 80s (1.0%). ethnicities. About 21% of breast cancers in NH black women are triple negative, which is about double the proportion of this subtype in other racial/ethnic Race/Ethnicity groups. The higher breast cancer death rate in black • Breast cancer incidence and death rates by race and women in part reflects the disproportionate burden ethnicity during the most recent time period are of triple negative breast cancers in this group. shown in Figure 3. Incidence rates are highest among non-Hispanic (NH) whites (130.8 per 100,000), Stage followed closely by NH blacks (126.7). However, NH black women have the highest breast cancer death • At the time of diagnosis, approximately 64% of breast rate (28.4 deaths per 100,000), more than double that cancer patients have local-stage breast cancer, in Asian/Pacific Islander (API) women (11.5), who 27% have regional stage, and 6% have distant have the lowest incidence and death rates. (metastatic) disease.

4 Breast Cancer Facts & Figures 2019-2020

Figure 3. Female Breast Cancer Incidence (2012-2016) Figure 4. Distribution of Breast Cancer Subtypes by and Death (2013-2017) Rates by Race/Ethnicity, US Race/Ethnicity, Ages 20 and Older, US, 2012-2016

150 Incidence Mortality HR/HER2- HR-/HER2 HR/HER2 HR-/HER2-

130.8 100 126.7 10 10 120 12 12 21 4 6 6 6 80 10 13 94.7 93.7 93.2 6 12 13 90 12 60

60 Rate per 100,000 per Rate Percent 40 76 70 69 71 61 30 28.4 20.3 20 14.6 14.0 11.5

0 Non-ispanic Non-ispanic American Indian/ ispanic/ Asian/ 0 White Black Alaska Native atina Pacific Islander Non-ispanic Non-ispanic American Indian/ ispanic Asian/ White Black Alaska Native Pacific Islander *Statistics based on data from PRCDA counties. Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. HR = hormone receptor, HER2 = human epidermal growth factor receptor 2. Sources: Incidence – NAACCR, 2019. Mortality – National Center for Health Statsitics based on data from PRCDA counties. Statistics (NCHS), Centers for Disease Control and Prevention, 2019. Source: NAACCR, 2019. ©2019, American Cancer Society, Inc., Surveillance Research ©2019, American Cancer Society, Inc., Surveillance Research

• Stage at diagnosis also varies by race/ethnicity (Figure In contrast, there was a sharp drop (nearly 13%) in the 5). NH black, Hispanic, and American Indian/Alaska invasive breast cancer rate between 1999 and 2004, Native (AIAN) patients are less likely to be diagnosed believed to be largely due to the decreased use of with local-stage disease (56%-60%) compared to NH menopausal following the 2002 publication of white and API patients (64%-66%). results that found higher risk of breast cancer and heart disease among menopausal hormone users, and may also reflect small declines in mammography How has the occurrence of breast screening since 2000.22, 23 The decline in breast cancer cancer changed over time? incidence occurred primarily in white women, in those 22, 24 Incidence 50 years of age and older, and for ER+ disease. Incidence rates of DCIS and invasive breast cancer rose In the most recent time period (2012-2016), the DCIS rate rapidly during the 1980s and 1990s (Figure 6), particularly declined by 2.1% per year8 and the invasive breast cancer among women 50 years of age and older, largely due to incidence rate rose by about 0.3% per year.20 In fact, the increases in the prevalence of mammography screening, incidence rate for invasive breast cancer has been slowly which increased from 29% in 1987 to 70% in 2000.21 increasing since 2004.20 A recent study concluded that For example, DCIS rates among women 50 and older, increases in (BMI) and declines in the increased more than 11-fold from 1980 (7 cases per average number of births per woman (both breast cancer 100,000) to 2008 (83 cases per 100,000). risk factors) have likely contributed to the recent increase in incidence.25

Breast Cancer Facts & Figures 2019-2020 5 2001-2011, but has since stabilized. The increase in Figure 5. Female Breast Cancer Stage Distribution, by distant-stage disease may be partly explained by the Race/Ethnicity, Ages 20 and Older, US, 2012-2016 decrease in unknown stage, because of more complete Localied Regional Distant nknown staging of advanced tumors.26 This trend may also reflect

100 increased detection of asymptomatic metastases due to 3 3 4 4 2 5 5 the rise in the use of advanced imaging. 8 6 6 90

80 26 28 Mortality 30 33 32 70 The overall breast cancer death rate increased by 0.4% per year from 1975 to 1989, but since has decreased 60 rapidly, for a total decline of 40% through 2017. As a

50 result, 375,900 breast cancer deaths were averted in US

Percent women from 1989 to 2017. However, the decline in breast 40 cancer mortality has slowed slightly in the most recent 66 64 30 60 time period, from an annual decrease of 1.9% during 56 58 1988-2011 to 1.3% during 2011-2017. By race/ethnicity, 20 the breast cancer death rate during 2013-2017 declined

10 annually by 2.1% in Hispanics, 1.5% in NH blacks, 1.0% in NH whites, and 0.8% in APIs, but was stable in AIANs 0 Non-ispanic Non-ispanic American Indian/ ispanic Asian/Pacific (Figure 8). White Black Alaska Native Islander *Statistics based on data from PRCDA counties. The decline in breast cancer mortality has been Source: NAACCR, 2019. ©2019, American Cancer Society, Inc., Surveillance Research attributed to both improvements in treatment and earlier detection.27 However, not all women have benefited equally from these advances, as indicated by the striking Race/Ethnicity divergence in mortality trends between black and white Figure 7 presents trends in invasive female breast cancer women beginning in the early 1980s (Figure 8). This incidence rates by race and ethnicity since 2001 based disparity likely reflects a combination of factors that are on data from 45 states, representing 92% of the US difficult to parse, including later stage at diagnosis and population. During the most recent 5 years of available other unfavorable tumor characteristics, higher data (2012 to 2016), overall breast cancer incidence rates prevelance of and other health conditions, less increased most rapidly among APIs (1.5% per year), access to high-quality prevention, early detection, and followed by AIANs (0.8% per year), and NH blacks and treatment.28, 29 For example, black women are more likely NH whites (both 0.5% per year), but were relatively stable to be screened at lower resourced and nonaccredited in Hispanics. facilities and also experience longer intervals between mammograms, and between abnormal results and Stage follow-up.30-33 Although self-reported screening rates The overall increase in breast cancer incidence is largely based on national surveys are similar between black and because of an increase in local-stage disease. From 2012 white women, studies indicate that black (and Hispanic) to 2016, the incidence rate increased by 1.1% per year for women are more likely than white women to local-stage breast cancer, but declined by 0.8% per year overestimate their screening history.34-36 The black-white for regional-stage disease, which may reflect a shift disparity has grown as treatment for breast cancers has toward earlier stage at diagnosis. The incidence rate for improved (particularly for HR+ breast cancers), but distant-stage disease increased 2.5% annually during appears to have peaked in 2011, when rates in NH black

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Figure 6. Trends in Incidence Rates of and Invasive Female Breast Cancer by Age, US, 1975-2016

a. DCIS Ages 20 b. Invasive 90 Ages 20-49 400 Ages 50 80 350

70 300

60 250 50 200 40 150

Rate per 100,000 per Rate 30 100,000 per Rate

100 20

10 50

0 0 1975 1980 1985 1990 1995 2000 2005 2010 2015 1975 1980 1985 1990 1995 2000 2005 2010 2015 Year Year

Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. Source: Surveillance, Epidemiology, and End Results (SEER) Program, SEER 9 Registries, National Cancer Institute, 2019. ©2019, American Cancer Society, Inc., Surveillance Research women were 44% higher than those in whites. In the most In contrast to incidence, breast cancer death rates are recent period (2013-2017), the breast cancer death rate higher among NH black women than NH white women in was 40% higher in black women versus white women every state, with rates in some states (e.g., Louisiana and (Figure 3). Mississippi) as much as 60% higher (Table 3). Death rates reflect both cancer incidence and survival. Breast cancer mortality rates among NH white women tend to be Are there geographic differences in highest in the North Central, Mid-Atlantic, and Western breast cancer patterns? regions of the US (Figure 9). Among NH black women, the Table 3 shows variation in state-level breast cancer highest death rates are found in some of the South Central incidence and death rates per 100,000 women by race/ and Mid-Atlantic states, as well as . Factors that ethnicity. Although the overall incidence rate for breast contribute to geographic disparities include variations in cancer in the US remains slightly higher in NH white risk factors and access to screening and treatment, which women compared to NH black women, rates are higher in are influenced by socioeconomic factors, legislative NH black women in 4 of the 43 states with reliable data policies, and proximity to medical services. for both groups (Louisiana, Mississippi, Oklahoma, and Wisconsin), and are not statistically different in 26 other During 2013-2017, breast cancer death rates decreased in states and the District of Columbia.37 Data for AIAN all states except Nebraska.37 In addition, the decline in women are too sparse to provide by state; however, breast cancer mortality has leveled off for black women during 2012-2016, incidence rates were more than two- in Colorado and Wisconsin and for white women in fold higher among women in Alaska (139.7 per 100,000) Nebraska, Texas, and Virginia. Notably, during 2016-2017, and the Southern Plains (150.8 per 100,000) compared to breast cancer was the leading cause of cancer deaths those living in the Southwest US (60.4 per 100,000).8 (surpassing cancer) in 6 states (Arizona, Colorado, , , Mississippi, and South Carolina) among black women and in Utah among white women.37

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Figure 7. Trends in Female Breast Cancer Incidence Figure 8. Trends in Female Breast Cancer Death Rates Rates by Race/Ethnicity, US, 2001-2016 by Race/Ethnicity, US, 1975-2017

140 NH white American Indian/Alaska Native 45 NH black Hispanic 120 Asian/Pacific Islander 40

100 35

80 30

25 60 NH white

Rate per 100,000 per Rate NH black 20 40 American Indian/Alaska Native Hispanic 100,000 per Rate 15 20 Asian/Pacific Islander 10

0 5 2001 2003 2005 2007 2009 2011 2013 2015 Year 0 NH indicates non-Hispanic. *Statistics based on data from PRCDA counties. 1975 1980 1985 1990 1995 2000 2005 2010 2015 Note: Rates are per 100,000 and age adjusted to the 2000 US standard Year population. Rates were adjusted for reporting delays. Source: NAACCR, 2019. Note: Rates are per 100,000 and age adjusted to the 2000 US standard © 2019, American Cancer Society, Inc., Surveillance Research population. Source: NCHS 2019. Rates for American Indian/Alaska Native are based on the PRCDA counties and are 3-year moving averages. © 2019, American Cancer Society, Inc., Surveillance Research Breast cancer survival Relative survival rates are an estimate of the percentage Stage at diagnosis of patients who will survive their cancer for a given period of time after diagnosis, accounting for normal life Stage at diagnosis is one of the most important factors expectancy. Survival among cancer patients is compared affecting prognosis. Five-year relative survival rates for to survival among people of the same age and race who breast cancer are: have not been diagnosed with cancer. • 99% for localized disease • 86% for regional disease Relative survival rates should be interpreted with caution because they are based on the average experience of all • 27% for patients diagnosed with metastatic disease20 women and do not predict individual prognosis because many patient and tumor characteristics that influence Breast cancer subtype (HR/HER2) breast cancer survival are not taken into account. In Breast cancer survival also varies by tumor subtype. addition, long-term survival rates are based on data from Five-year relative survival rates are: patients diagnosed and treated many years ago and thus, do not reflect more recent improvements in early • 92% for HR+/HER2- detection and treatment. • 89% for HR+/HER2+

Based on the most recent data, relative survival rates for • 83% for HR-/HER2+ women diagnosed with breast cancer are: • 77% for HR-/HER2- • 91% at 5 years after diagnosis Importantly, a recent study found that 4-year relative • 84% after 10 years survival was 95% or greater for patients diagnosed with • 80% after 15 years stage I breast cancers across all breast cancer subtypes.11

8 Breast Cancer Facts & Figures 2019-2020 Table 3. Female Breast Cancer Incidence and Death Rates by Race/Ethnicity and State Incidence Rates (2012-2016) Death Rates (2013-2017) Non- Non- Asian/ Non- Non- Asian/ Hispanic Hispanic Pacific Hispanic Hispanic Pacific State White Black Hispanic Islander White Black Hispanic Islander Alabama 121.2 125.7 57.1 81.5 20.0 26.8 * * Alaska 122.5 132.0 111.0 77.6 19.5 * * * Arizona 122.1 111.7 91.9 80.4 20.0 26.0 15.2 12.1 Arkansas 116.3 118.3 92.2 117.3 19.9 29.5 13.2 * California 138.8 128.1 91.4 98.0 22.2 30.9 14.4 12.9 Colorado 130.0 120.2 106.4 75.4 19.1 28.7 17.2 7.7 Connecticut 144.3 127.2 122.6 88.2 18.0 21.8 12.2 8.2 Delaware 139.1 135.7 101.6 92.3 21.2 24.8 * * District of Columbia† 139.9 135.5 69.9 86.3 18.1 33.2 * * Florida 123.4 110.1 99.2 75.4 19.5 25.6 14.2 9.9 Georgia 127.2 129.3 103.0 84.0 20.0 28.6 11.6 10.0 Hawaii 147.0 110.7 150.8 134.7 20.2 * 22.0 14.5 Idaho 125.7 * 94.7 86.2 22.4 * 13.1 * 138.0 135.3 93.0 94.6 21.2 30.2 11.5 11.5 Indiana 123.1 129.1 91.5 71.2 20.6 28.3 14.0 * Iowa 126.1 112.6 67.0 81.7 18.7 20.3 12.6 * Kansas 127.8 125.4 88.5 73.6 19.2 28.3 11.9 * Kentucky 127.2 128.3 71.5 73.3 21.1 25.2 * * Louisiana 122.8 134.7 90.1 69.0 19.9 32.3 9.6 * Maine 126.1 * 82.5 75.4 18.5 * * * 136.7 133.2 92.6 88.5 20.3 28.2 10.0 9.8 Massachusetts 143.3 120.7 88.2 93.1 18.1 20.1 11.5 7.9 124.7 127.0 76.9 86.5 20.0 28.8 13.6 9.2 Minnesota 132.4 102.0 111.6 74.7 18.1 20.3 11.0 7.8 Mississippi 116.4 122.2 44.9 76.7 19.8 31.6 * * Missouri 130.0 133.7 76.3 94.3 20.8 30.5 10.8 12.1 Montana 124.0 * 125.0 115.7 19.9 * * * Nebraska 127.8 107.5 93.2 57.7 20.6 25.8 * * Nevada† 120.9 109.5 79.4 80.1 23.9 29.7 12.0 15.0 New Hampshire 146.4 94.0 95.0 88.3 19.3 * * * New Jersey 143.2 132.2 105.8 96.5 21.6 31.0 12.9 10.4 New Mexico 123.0 110.8 102.0 75.3 21.8 * 17.3 * 141.9 121.7 102.3 94.1 19.4 25.3 13.4 9.8 134.8 133.9 81.5 80.7 19.5 27.8 10.4 11.2 North Dakota 127.5 * * * 18.2 * * * Ohio 128.8 128.4 64.9 82.1 21.7 29.8 11.6 10.7 Oklahoma 118.2 126.9 91.3 83.7 22.5 31.3 11.9 * Oregon 127.8 127.6 97.0 86.2 20.6 27.9 13.2 10.2 134.8 130.5 91.9 75.6 20.7 30.8 11.1 10.3 Rhode Island 144.1 118.9 86.6 85.3 18.2 24.8 * * South Carolina 130.9 128.6 91.2 73.8 19.7 28.0 8.4 * South Dakota 132.6 * * * 19.3 * * * Tennessee 123.8 124.8 70.7 72.6 20.6 29.8 13.4 13.2 Texas 123.5 120.9 89.1 71.3 20.5 28.5 15.5 10.1 Utah 116.4 80.6 106.5 96.2 20.8 * 11.1 15.0 Vermont 132.6 * * * 17.9 * * * Virginia 131.8 134.6 79.0 79.3 21.0 28.9 10.0 9.5 Washington 139.1 124.1 101.1 99.7 20.9 22.8 10.4 11.9 West Virginia 117.5 128.2 * 94.7 21.8 31.2 * * Wisconsin 132.0 141.1 82.6 78.9 19.0 28.0 7.9 * Wyoming 114.9 * 83.0 * 18.5 * * * 130.8 126.7 93.7 93.2 20.3 28.4 14.0 11.5 Note: Rates are per 100,000 and age adjusted to 2000 US standard population. *Statistic not displayed due to fewer than 25 cases or deaths. †This registry did not achieve high-quality data standards for one or more years during 2012-2016 and are not included in the overall US incidence rate. Sources: Incidence: NAACCR, 2019. Mortality: NCHS, 2019. © 2019, American Cancer Society, Surveillance Research

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Figure 9. Geographic ariation in Female Breast Cancer Death Rates by Race/Ethnicity, 2013-2017

Non-Hispanic Whites

WA

MT ND ME

OR MN VT ID NH SD MA WI NY WY MI RI CT IA PA NV NE NJ OH UT IL IN DE CA CO WV MD KS VA MO KY DC

NC TN AZ OK NM AR SC

MS Deaths per 100,000 AL GA 17.9- 18.7 AK 18.8 - 19.6 TX LA 19.7 - 20.4 20.5 - 21.1 FL 21.2 - 23.9

HI

Non-Hispanic Blacks

WA

MT ND ME

OR MN VT ID NH SD MA WI NY WY MI RI CT IA PA NV NE NJ OH UT IL IN DE CA CO WV MD KS VA MO KY DC

NC TN AZ OK NM AR SC Deaths per 100,000 MS AL GA 20.1 - 24.9 AK 25.0 - 27.9 TX LA 28.0 - 28.7 28.8 - 30.5

FL 30.6 - 33.2 Data not shown HI

Note: Rates are per 100,000 and age adjusted to the 2000 US standard population. *Statistic not displayed for states with fewer than 25 deaths during 2013-2017. Source: NCHS, 2019. ©2019, American Cancer Society, Inc., Surveillance Research

10 Breast Cancer Facts & Figures 2019-2020 Race/ethnicity Figure 10. Trends in Female Breast Cancer 5-year Five-year relative survival has improved from 76% in Relative Survival Rates by Race, US, 1975-2015 1975-1977 to 92% in 2009-2015 in white women and from 100 hite Black 62% to 83% over the same time period in black women (Figure 10). While the racial disparity has narrowed, there 90 remains a substantial gap, especially for late-stage 80 diagnoses (Figure 11). 70

Cause-specific survival instead of relative survival is used 60 to describe the cancer experience of racial and ethnic 50 minorities because reliable life expectancy is not Percent historically available for some groups. Cause-specific 40 survival is the probability of not dying of breast cancer 30 within five years of diagnosis. For every stage at diagnosis, API women have the highest breast cancer survival and 20

NH black women have the lowest (Figure 11). Poverty, less 10 education, and a lack of are associated 38, 39 0 with lower breast cancer survival. Of note, high 1975- 1978- 1981- 1984- 1987- 1990- 1993- 1996- 1999- 2002- 2005- 2009- 1977 1980 1983 1986 1989 1992 1995 1998 2001 2004 2008 2015 survival rates for API and Hispanic patients are probably Year overestimated because of incomplete or inaccurate Source: SEER Program, 18 SEER registries, National Cancer Institute, 2019. follow-up information in cancer registry data.40 ©2019, American Cancer Society, Inc., Surveillance Research

Figure 11. Five-year Breast Cancer-specific Survival Rates (%) by Stage at Diagnosis and Race/Ethnicity, US, 2009-2015

100 97 98 95 96 93 NH white NH black 90 89 86 85 85 American Indian/Alaska Native Hispanic 80 78 Asian/Pacific Islander

70 64 62 60 57 56 55

50 Percent 40 33 34 31 30 29

21 20

10

0 ocalied Regional Distant Unstaged

Survival rates are based on patients diagnosed during 2009-2015 and followed through 2016. Source: SEER Program, 18 SEER registries, National Cancer Institute, 2019. ©2019, American Cancer Society, Inc., Surveillance Research

Breast Cancer Facts & Figures 2019-2020 11 Due to the infrequency of male breast cancer, much less is known about the disease. Similar to women, male Breast cancer in men is rare, accounting for less than 1% breast cancer risk increases with age. Other risk factors of breast cancer cases in the US. However, since 1975, the include exposure, BRCA1/2 gene , incidence rate has increased slightly, from 1.0 case per family history of breast or , Klinefelter 100,000 men during 1975-1979 to 1.2 cases per 100,000 syndrome, testicular disorders, , men during 2012-2016.41 Men are more likely than women (enlarged ), and obesity.44, 45 In contrast to female (51% versus 36%) to be diagnosed with advanced breast cancer, studies have found that smoking, alcohol (regional- or distant-stage) breast cancer,8 which likely consumption, and physical inactivity are not linked to reflects delayed detection because of decreased male breast cancer.46, 47 awareness.42 The death rate for male breast cancer has decreased slightly from 0.4 deaths per 100,000 men during 1975-1979 to 0.3 per 100,000 men during 2013- 2017,43 reflecting improvements in treatment.

Breast Cancer Risk Factors The most well-established risk factors for breast cancer Family history and personal are summarized in Table 4. It is estimated that about characteristics one-third of postmenopausal breast cancers are linked to potentially modifiable factors, including postmenopausal Family history obesity, physical inactivity, use of combined estrogen and Women (and men) with a family history of breast cancer, progestin menopausal hormones, alcohol consumption, especially in a first-degree relative (parent, child, or and not .48 Many risk factors (early sibling), are at increased risk for the disease. Compared , late , obesity, and hormone use) to women without a family history, risk of breast cancer affect lifetime exposure of breast tissue to hormones. is about 1.5 times higher for women with one affected Hormones are thought to influence breast cancer risk by first-degree female relative and 2-4 times higher for increasing cell division, thereby increasing the likelihood women with more than one first-degree relative.51-53 Risk of DNA damage, as well as promoting cancer growth. is further increased when the affected female relative was Although exposures that influence risk accumulate diagnosed at a young age or was diagnosed with cancer throughout a woman’s life, research suggests that early- in both breasts, or if the affected relative is male. It is life exposures during may be important to note that the majority of women with one or particularly critical.49 Many established risk factors for more affected first-degree relatives will never develop breast cancer are specifically associated with HR+/ breast cancer and that most women who develop breast luminal breast cancer; less is known about risk factors cancer do not have a family history of the disease.51 for HR-, HER2+ or basal-like breast cancers.50 The following sections present current knowledge about A family history of ovarian and perhaps pancreatic or factors associated with breast cancer risk. is also associated with increased breast cancer risk.54, 55 Women should discuss their family history with their health care provider because it may signal the presence of a genetic predisposition to cancer and the need for a different plan for screening and risk reduction.

12 Breast Cancer Facts & Figures 2019-2020 Compared to women in the general population who have a Table 4. Factors That Increase the Relative Risk for 10% risk of developing breast cancer by 80 years of age, risk Invasive Breast Cancer in Women is estimated to be about 70% in women with pathogenic 61 Relative variants in BRCA1 and BRCA2. The risk of breast cancer >4.0 Age (65+ versus <65 years, although risk increases by age 70 in women with pathogenic variations in PALB2, across all ages until age 80) Atypical a different gene that works with BRCA2, is estimated to 62 Lobular carcinoma in situ be 35%. Mutations in other genes are also associated Pathogenic genetic variations (e.g. BRCA1, with increased breast cancer risk, including TP53 BRCA2, PALB2, TP53) (associated with Li-Fraumeni syndrome), PTEN (Cowden 2.1-4.0 Ductal carcinoma in situ High endogenous hormone levels (postmenopausal) syndrome), STK11 (Peutz-Jeghers syndrome), and CDH1 High-dose radiation to chest (e.g. Hodgkin lymphoma (associated with diffuse gastric and lobular breast cancer treatment) syndrome). In addition, research studies have identified Mammographically dense breasts Two or more first-degree relatives with breast cancer more than 300 more common genetic variants that are 63 1.1-2.0 Alcohol consumption associated with slightly elevated risk. Early menarche (<11 years) Excess body weight The US Preventive Services Task Force recommends that High endogenous estrogen or levels (premenopausal) primary care providers routinely collect and update Late age at first full-term (>30 years) family medical history, as well as ancestry. Women with a Late menopause (≥55 years) personal or family history of breast, ovarian, tubal, or Never breastfed a child peritoneal cancer or those with ancestry associated with No full-term BRCA1/2 gene mutations should be screened with one of One first-degree relative with breast cancer Obesity (postmenopausal) several brief questionnaires to determine if there is a Personal history of ovarian or need for in-depth to consider genetic Physical inactivity testing.64 Those who consider testing are strongly Proliferative without atypia (usual ductal hyperplasia, ) encouraged to talk with a genetic counselor before making Recent and long-term use of menopausal hormone a decision so that the benefits and potential consequences therapy containing estrogen and progestin can be understood and carefully considered. Recent hormonal contraceptive use Weight gain in adulthood Tall height Personal history of breast cancer Note: Relative risks for some factors vary by breast cancer molecular subtype. Women diagnosed with breast cancer have a small increased risk of developing a new cancer, with estimated Genetic predisposition 10-year risks ranging from 3%-7%.65 However, rates of subsequent new breast cancers (also referred to as a new Inherited pathogenic (disease-causing) genetic variations primary breast cancer) have declined steadily since 1985.66 in BRCA1 and BRCA2, the most well-studied breast The decrease has predominantly been among ER+ breast cancer susceptibility genes, account for 5%-10% of all cancer patients and may reflect the effect of hormonal female breast cancers and 15%-20% of all familial breast therapy (e.g., and inhibitors) and cancers.56, 57 These variations are rare (about 1 in 400) in other adjuvant treatments, as well as the rapid increase the general population, but occur slightly more often in in breast cancer patients electing bilateral certain ethnic or geographically isolated groups, such as for breast cancer treatment (see page 23).65, 67 those of Ashkenazi (Eastern European) Jewish descent (about 1 in 40). Recent studies also document increased frequency of BRCA mutations among black and Hispanic DCIS and LCIS breast cancer patients.58-60 DCIS is considered a potential precursor to invasive cancer and risk of subsequent breast cancer is greatest at or near the site of DCIS.68 Similar to women with a prior

Breast Cancer Facts & Figures 2019-2020 13 In contrast, LCIS is not generally considered a breast What is the difference between absolute, cancer precursor, but is associated with increased risk lifetime, and relative risks? of developing breast cancer. A recent population-based Absolute risk is the likelihood of being diagnosed study of US women diagnosed with LCIS between 1983 with cancer over a certain period of time. For example, and 2014 reported that the 10- and 20-year risk of being the absolute risk of breast cancer increases with diagnosed with DCIS or an invasive breast cancer was age: 12 out of 10,000 women ages 40-44 versus 11% and 20%, respectively.71 Notably, the study also 23 out of 10,000 women ages 50-54 will be diagnosed with breast cancer in the next year.8 reported that the 20-year breast cancer survival in those diagnosed with DCIS or invasive breast cancer exceeded Lifetime risk is the absolute risk of being diagnosed 95%. Pleomorphic LCIS, a more aggressive subtype, is with cancer anytime between birth and death. linked to a higher risk of invasive cancer than classic Lifetime risk of breast cancer reflects the average LCIS and is often treated as though it is a cancer probability of a female being diagnosed with breast precursor.72 cancer in the US. A woman living in the US has a 13% chance of being diagnosed with invasive breast cancer in her lifetime (Table 2). Another way Benign breast disease to say this is that 1 out of every 8 women will be Benign breast conditions are categorized into 3 general diagnosed with breast cancer in her lifetime. groups reflecting the associated degree of cancer risk: Relative risk compares the absolute risk of disease nonproliferative lesions, proliferative lesions without among people with a particular risk factor to the risk atypia (abnormal cells or patterns of cells), and among people without that risk factor. If the relative proliferative lesions with atypia. risk is above 1.0, then risk is higher among those with the risk factor than among those without the factor. • Nonproliferative lesions are not associated with Relative risks below 1.0 reflect an inverse association overgrowth of breast tissue and include fibrosis and between the exposure and the disease, or a protective effect. For example, one study found women ages 50-59 simple (also known as fibrocystic changes) who were current users of combined estrogen and and mild hyperplasia. Nonproliferative conditions progestin menopausal hormones had a relative risk of are associated with little to no increased breast developing breast cancer of 1.21, meaning they had a cancer risk.73 21% increased risk compared to women who have not used .69 While relative risks are useful • Proliferative lesions without atypia are associated for comparisons, they do not provide information about with a small increase in the risk of breast cancer the absolute risk of the exposed group. In this example, (1.5 to 2 times the risk of those who do not have one 27 breast cancers per year would be expected to be of these lesions) and include usual ductal hyperplasia diagnosed among 10,000 women ages 50-59 who had (without atypia) and fibroadenoma.73 never used menopausal hormones (their absolute risk) compared to 33 breast cancers among 10,000 women • Proliferative lesions with atypia are associated with of the same ages who had used estrogen and progestin. about 4 times higher than average breast cancer risk. Thus, the 21% increased relative risk is the equivalent of These include atypical ductal hyperplasia and 6 additional breast cancers per 10,000 women per year. atypical lobular hyperplasia.73, 74 Recent studies indicate that the 15-year risk of developing in situ invasive breast cancer, women diagnosed with DCIS have or invasive breast cancer exceeds 30% in women 74, 75 a small increased risk for developing a new breast cancer. diagnosed with atypical hyperplasia. A recent study estimated that 3%-5% of women diagnosed with DCIS were diagnosed with in situ or invasive breast Women should keep detailed records of any benign cancer in the opposite breast within 10 years of their results because they are valuable for initial diagnosis.70 risk assessment, screening, and counseling for chemoprevention and other risk-reduction strategies.

14 Breast Cancer Facts & Figures 2019-2020 Breast density Height Breast tissue density is an indicator of the amount of Many studies have found that taller women have a higher glandular and relative to fatty tissue risk of breast cancer than shorter women.83-85 A pooled measured during a mammogram and is not determined study of more than 5 million women estimated that by how “firm” the breast feels. Following a mammogram, an increase of 10 cm (about 4 inches) in height was doctors categorize a woman’s breast tissue according to associated with about a 17% higher risk of breast standardized system developed by the American College cancer.84 Although the reasons are not fully understood, of called the Breast Imagine Reporting and it may reflect differences in early growth as well as Data System (BI-RADS) as A) fatty; B) scattered areas of hormonal or genetic factors. Height is also associated fibroglandular tissue; C) heterogeneously dense; and D) with a number of other cancers, including colorectal extremely dense. Women with breasts classified as C and ovarian cancers. (heterogeneously dense) or D (extremely dense) are referred to as having “dense breasts.” The risk of breast Menstrual cycles cancer increases with increasing breast density. Women Breast cancer risk increases with earlier menstruation with dense breasts (BI-RADS C or D) have a 1.5- to 2-fold and later menopause.86 For example, breast cancer risk is increased risk of breast cancer compared to those with about 20% higher among those who begin menstruating average density (BI-RADS B).76 High breast density can before age 11 compared to those who begin at age 14 or also mask the appearance of breast tumors on a older. Likewise, women who experience menopause at mammogram.77 age 55 or older have about a 12% higher risk compared to those who do so between ages 50-54.86 The increased risk Dense breasts are common. About 36% of US women may be due to longer lifetime exposure to reproductive ages 40-74 have heterogeneously dense breasts and hormones and has been more strongly linked to HR+ about 7% have extremely dense breasts (BI-RADS C or D, breast cancer than other subtypes.50 respectively).78 Breast density is influenced by genetics and other factors. For most women, breast density generally decreases with age, higher body weight, and after pregnancy mineral density and menopause.79 Some drugs also affect breast density, High bone mineral density in postmenopausal women including tamoxifen (decreases density) and combined has been associated with a 60%-80% increased risk for menopausal hormone therapy (increases density).79, 80 breast cancer compared to low bone density; risk appears to be most strongly related to HR+ disease.87, 88 Bone In early 2019, the US Food and Drug Administration density is not thought to be an independent risk factor proposed a federal rule that mammogram reports for breast cancer, but a marker of cumulative estrogen include information about breast density. Thirty-eight exposure.89 However, because bone density is routinely states and the District of Columbia previously passed measured to identify women at increased risk for some form of breast density legislation. Some state laws (high bone density indicates absence of require that women with dense breasts be told that they osteoporosis); it also may be helpful for identifying may benefit from supplemental imaging tests, such as women at increased risk for breast cancer. or MRI. However, there is currently no expert consensus about what other tests, if any, should be done Endogenous hormone levels in addition to mammograms to screen for breast cancer Postmenopausal women with naturally high levels of in women with dense breasts.81 Ongoing clinical trials are certain endogenous sex hormones (e.g., estrogen, evaluating whether digital breast (DBT) progesterone) have about twice the risk of developing or MRI may be more useful than conventional digital breast cancer compared to women with the lowest levels, mammography in evaluating dense breasts.82 See page 20 with the strongest relationships found for HR+ tumors.90, 91 for more information on DBT.

Breast Cancer Facts & Figures 2019-2020 15 High circulating hormone levels are associated with, and Breastfeeding may reflect, the effects of other breast cancer risk factors, Most studies suggest that breastfeeding for a year or such as postmenopausal obesity and alcohol use.91 more slightly reduces a woman’s overall risk of breast Although it is challenging to study the relationship of cancer, with longer duration associated with greater risk hormones in premenopausal women because levels vary reduction. In a review of 47 studies in 30 countries, the across the , there is some evidence that risk of breast cancer was reduced by 4% for every 12 high levels of circulating and androgens are months of breastfeeding.101 The protective effect may be associated with a small excess risk in premenopausal stronger for – or even limited to – triple negative women, particularly for HR+ breast cancer.91-93 cancers.102-104

Reproductive factors Hormonal Pregnancy Most studies have found that current or recent use of oral contraceptives (combined estrogen and progesterone) is Pregnancy has a dual effect on breast cancer risk.94 associated with a small (about 20%) relative increase in In the short term, women who have had a full-term breast cancer risk, particularly among women who begin pregnancy have an increased risk of both HR+ and HR- use before first pregnancy.105, 106 Risk appears to diminish breast cancers that peaks at 5 years after childbirth. when women stop use, and after about 10 years, it is However, after about two decades, the relative risk of similar to those who have never taken oral contraceptives. HR+ breast cancer becomes slightly lower (by about Notably, data are limited and less clear for “ultra low- 20%-25%) in women who have given birth compared to dose” (20 micrograms) estrogen formulations.107 those who have not. Risk is further reduced among women who have their first child at a younger age or Studies of the -releasing intrauterine have a greater number of children. In contrast, the device (Mirena) have produced conflicting results, but a increased risk for HR- breast cancer persists following large study from found that use of Mirena also a full-term pregnancy. increases breast cancer risk by about 20%.105, 108-110 In contrast, the use of the injectable progestin-only Fertility drugs contraceptive depot-medroxyprogesterone acetate More research is needed on the relationship between (Depo-Provera) does not seem to be linked with breast breast cancer risk and the long-term effects of ovulation- cancer.105, 111 Overall, it has been estimated that one extra stimulating drugs.95 Most studies to date have found breast cancer is diagnosed for every 7,690 women using that breast cancer risk is not elevated in women who for one year.105 undergo fertilization.96-100 However, the data are less clear for clomiphene (Clomid), a drug that is often Postmenopausal hormones used as a first-line treatment for infertility.97, 99, 100 A Recent use of menopausal hormones (also referred to as long-term follow-up study of women seen at 5 US fertility hormone therapy or hormone replacement therapy) with clinics found no association with ever use of Clomid or combined estrogen and progestin increases the risk of HR+ gonadotropins; however, risk of invasive breast cancer breast cancer, with higher risk associated with longer was increased among women who underwent more than use.50, 69, 112, 113 Risk appears to be greater for women who 12 Clomid treatment cycles compared to women who had start hormone therapy soon after the onset of menopause never used fertility drugs.100 Another recent study from compared to those who begin later.113, 114 Discontinuation Norway reported that use of Clomid was linked to a of menopausal hormones diminishes but does not slightly increased risk of breast cancer, but only among eliminate the increase in breast cancer risk.115 Combined women who had given birth.99 hormone therapy also increases breast density.80

16 Breast Cancer Facts & Figures 2019-2020 Postmenopausal estrogen-only therapy has been menopause is associated with reduced breast cancer risk associated with uterine problems (including endometrial in some, but not all studies.123, 126 The effects of weight loss cancer) and is therefore only given to women who have are more difficult to examine because it is often not undergone . The effects of estrogen-only sustained. therapy on breast cancer risk is less clear, but they are likely minimal at most. The Women’s Health Initiative In contrast, studies have found that excess body weight randomized trial116 found that women who used protects against premenopausal breast cancer. A large estrogen-only therapy for an average of 6 years had a 25% meta-analysis found that among women between 40 and lower risk of developing breast cancer, but several 49 years of age, the risk for developing breast cancer was observational studies have found a slight increase in about 14% lower in overweight women and 26% lower in breast cancer risk among estrogen therapy users, obese women compared to women who were normal particularly among lean women and those who begin weight.127 The underlying mechanisms for this inverse therapy soon after menopause.114, 117, 118 Conflicting results relationship are not well understood.123 may reflect differences between studies in the prevalence of obesity or higher rates of screening in menopausal Physical inactivity hormone users in the observational studies.119 Women who get regular physical activity have a 10%-20% lower risk of breast cancer compared to women who are Recently reported results after 18 years of follow-up of inactive, with greater risk reduction associated with the Women’s Health Initiative randomized trial found no increasing levels of activity.128-131 The protective effect is increased risk of death overall or due to breast cancer independent of BMI and may be limited to women who associated with use of estrogen plus progestin or have never used menopausal hormone therapy.131 The estrogen alone.120 benefit may be due to the effects of physical activity on systemic inflammation, hormone levels, and energy Excess body weight, physical balance.131, 132 inactivity, diet, alcohol, and tobacco Diet Excess body weight and weight gain Numerous studies have examined the relationship Postmenopausal HR+ breast cancer risk is about 1.5-2 between food consumption (including , fiber, soy, times higher in women who are overweight or obese.121 dairy, meat, and fruits and vegetables) and breast cancer Even within the normal range of BMI (18.5-24.9), higher with mixed results. A recent meta-analysis concluded levels of body fat are associated with increased risk of there was no association between breast cancer and breast cancer after menopause.122 This is likely due, in dietary fat consumption.133 It has been suggested that soy part, to higher estrogen levels because fat tissue is the consumption may reduce breast cancer risk, in part largest source of estrogen in postmenopausal women, but because of historically low breast cancer rates among may also be related to other mechanisms, including the Asian women, who have a diet high in soy. A meta- higher levels of among women with excess body analysis showed that soy intake was inversely associated weight.122, 123 with breast cancer risk in Asian but not Western populations, perhaps because Asian women generally Weight gain also increases risk of postmenopausal consume more soy products beginning at an earlier age breast cancer.124, 125 A large meta-analysis found that for than Western women.134 each 5 kilograms (about 11 pounds) gained during adulthood, risk of postmenopausal breast cancer There is limited but growing evidence that high levels of increases by 11%.125 Notably, the increased risk was only fruit and/or vegetable consumption may reduce the risk observed among women who did not use menopausal of HR- breast cancer.135-137 These findings are supported hormones. Weight loss in early adulthood and after by studies linking lower breast cancer risk to higher

Breast Cancer Facts & Figures 2019-2020 17 blood levels of (micronutrients found in susceptible to before it is fully differentiated, fruits and vegetables).138-140 Studies also suggest that which occurs with first childbirth. Breast cancer risk calcium-rich diets may be linked to lower risk of breast starts to rise about 8 years after radiation treatment and cancer.136 The effect of diet on breast cancer risk remains continues to be elevated for more than 35 years.149 an active area of research, with studies particularly Although radiation treatments have evolved to include focused on the timing of exposure, specific dietary lower doses given over smaller areas, recent studies components, and risk differences by tumor hormone suggest that the elevated breast cancer risk persists.150 receptor status. (DES) exposure Alcohol From the 1940s through 1971, some pregnant women Numerous studies have confirmed that alcohol were given the drug DES because it was thought to lower consumption increases the risk of breast cancer in the risk of . These women have an increased women by about 7%-10% for each 10 grams (roughly one risk (about 30%) of developing breast cancer compared to drink) of alcohol consumed per day on average.141 Women women who have not taken DES.151 It remains unclear who have 2-3 alcoholic drinks per day have a 20% higher whether women born to mothers who took DES also have risk of breast cancer compared to non-drinkers. There is a higher risk.151-153 also some evidence that alcohol consumption before first pregnancy may particularly affect risk.141, 142 Although Environmental chemicals and pollutants mechanisms are not well understood, alcohol may Many occupational, environmental, and chemical increase risk indirectly by increasing estrogen and other exposures have been proposed as causes of breast cancer. hormone levels.143 Alcohol use appears more strongly In general, epidemiological studies have not found clear associated with risk for HR+ than HR- breast cancers.50, 144 relationships between environmental pollutants, such as organochlorine pesticides, and breast cancer. Studies to Tobacco date have found no association between increased Accumulating research indicates that smoking may concentrations of organochlorines (e.g., dichlorodiphenyl slightly increase breast cancer risk, particularly long- trichloroethane, or DDT) in blood and fat tissue of adults term, heavy smoking and among women who start and breast cancer risk,154 although a recent study found smoking before their first pregnancy.145, 146 A review by in utero exposure to DDT was linked to elevated breast American Cancer Society researchers found that women cancer risk later in life.155 Animal studies have demonstrated who initiated smoking more than 10 years before the that prolonged, high-dose exposure to many chemicals birth of their first child had a 18% higher risk of breast can increase development, but it is cancer than women who never smoked.146 Some studies unknown whether the much lower dose exposures that suggest secondhand smoke may increase risk, particularly occur in the general environment increase human breast when exposure happens in childhood and for cancer risk. Furthermore, many relevant chemicals have premenopausal breast cancer.147-148 not been adequately studied in humans and this is an active area of research.156-158 Environmental and other risk factors Night Radiation Most studies of nurses who work night shifts and flight Radiation exposure has been shown to increase breast attendants who experience disruption cancer risk in studies of atomic bomb survivors and caused by crossing multiple time zones have found females treated with high-dose to the increased risks of breast cancer associated with long- chest between 10 and 30 years of age, such as for Hodgkin term employment.159, 160 Elevated risk appears to be most lymphoma. This may be because breast tissue is most strongly associated with shift working during early

18 Breast Cancer Facts & Figures 2019-2020 adulthood.161, 162 Exposure to light at night disrupts the Chemoprevention and prophylactic production of melatonin, a hormone that regulates sleep. Experimental evidence suggests that melatonin may also inhibit the growth of small, established tumors and Chemoprevention prevent new tumors from developing.163 Based on the The use of drugs to reduce the risk of disease is called results of studies in humans and animals, the chemoprevention. Currently, the US Food and Drug International Agency for Research on Cancer has Administration has approved two drugs to help lower the concluded that shift work, particularly at night, is risk of breast cancer in high-risk women: tamoxifen and probably carcinogenic to humans.164 (postmenopausal women only). These drugs are classified as selective modulators Factors that are not associated (SERMs) because they block estrogen in some tissues of the body, but act like estrogen in others. with breast cancer risk A large meta-analysis, including more than 83,000 There are persistent claims that women who have had high-risk women, found that SERMs reduced breast 169 an abortion are at increased risk for developing breast cancer risk by 38% over 10 years. Although the benefit cancer based on early studies that have since been is limited to ER+ disease, these drugs lower the risk of deemed methodologically flawed by the American both invasive cancer and DCIS. However, SERMs are College of Obstetricians and Gynecology.165 Indeed, a associated with some side effects, including hot flashes, large body of solid scientific evidence, including a review , and fatigue. Premenopausal women taking by a panel of experts convened by the National Cancer tamoxifen can also experience menstrual changes. More Institute in 2003, confirms that there is no link between serious side effects are rare but include blood clots and 169 breast cancer and abortion (either spontaneous or endometrial cancer. induced).166 Clinical trials have shown that another class of drugs – aromatase inhibitors – also reduce breast cancer risk (by more than half) among high-risk postmenopausal Although internet rumors have suggested that bras cause women.170 As a result, the US Preventive Services Task breast cancer by obstructing lymph flow, there is no Force recently expanded their recommendations to scientific basis or evidence to support this claim. A recent include aromatase inhibitors, as well as SERMS, for population-based study of more than 1,500 women found breast cancer risk reduction in high-risk women.171 no association between wearing a and breast cancer.167 Aromatase inhibitors can decrease bone density, so women taking these drugs must be monitored for Breast implants osteoporosis. No association has been found between breast implants and risk of breast cancer; however, there is evidence that women with implants are at increased risk of a rare type Women at very high risk of breast cancer (such as of lymphoma.168 In addition, breast implants can obstruct those with pathogenic BRCA gene variants) may elect the view of breast tissue during mammography. Women prophylactic (preventive) mastectomy. Removal of both with breast implants should inform the mammography breasts reduces the risk of breast cancer by 90% or facility about the implants during scheduling so that more.172 Prophylactic salpingo- (surgical additional x-ray pictures (called displacement removal of the fallopian tubes and ) reduces the views) may be used to allow for more complete breast risk of ovarian cancer, but the benefit for breast cancer imaging. in high-risk women is less clear and may be limited to

Breast Cancer Facts & Figures 2019-2020 19 BRCA2 mutation carriers.173 Importantly, however, many doctor, and a second opinion is strongly recommended. women who elect prophylactic surgery would not have See page 23 for further discussion of contralateral developed cancer. Women considering these options prophylactic mastectomy in women diagnosed with should discuss the benefits and limitations with their unilateral breast cancer.

Breast

American Cancer Society recommendations for the early lesions detected by mammography, particularly DCIS, detection of breast cancer vary depending on a woman’s would not have progressed or otherwise been detected age and include mammography, as well as magnetic without screening. Estimates of the prevalence of resonance imaging (MRI) for women at high risk. The vary widely because it cannot be directly recommendations for average-risk women were most measured.180 Mammography may also result in false- recently updated in 2015 (see box, opposite page);174 positive results, which lead to follow-up examinations, recommendations for women at increased risk will be including , when there is no cancer; false updated in 2020. positives are more likely when women have their first screening. About 12% of women screened with modern digital mammography require follow-up imaging or Mammography biopsy, but most (95%) of these women do not have Mammography is a low-dose x-ray image of breast tissue. cancer.181 Cummulative radiation exposure from Although early mammographic images were on x-ray repeated mammograms may slightly increase the risk of film, digital technology, in which a 2-dimensional (2D) breast cancer;182 however, the dose of radiation during a image of breast tissue is captured electronically and mammogram is relatively small and the benefit of viewed on a monitor, has largely replaced screen-film screening likely outweighs any harm. Reducing radiation mammography. Digital mammography has improved exposure through more effective imaging is an area of sensitivity for women under age 50 and those with dense current research. breast tissue.175 The Affordable Care Act requires that and all Early detection of breast cancer by mammography reduces new private health insurance plans fully cover screening the risk of breast cancer death and increases treatment mammograms without any out-of-pocket expense for options, including less extensive surgery and/or the use of patients. There are also programs, such as the CDC’s with fewer side effects, and sometimes, the National Breast and Early Detection option to forgo chemotherapy. Combined analysis of breast Program, that offer mammography services for low-income, cancer screening in randomized trials has demonstrated uninsured, and underserved women. For help locating a an overall reduction in breast cancer deaths of about free or low-cost screening mammogram in your area, 20%.176 More recent results from organized mammography contact the American Cancer Society at 1-800-227-2345. programs in Europe and indicate that the risk of breast cancer death was reduced by more than 40% among Digital breast tomosynthesis (DBT) women who were screened.177-179 In 2011, the FDA approved the use of DBT (also referred to as 3D mammography) for . DBT Women should also be informed of the limitations of takes multiple breast images, in combination with digital mammography. Mammography will not detect all breast 2D mammography, which can be used to construct a 3D cancers, and some breast cancers detected by screening image of the breast. Some studies have found that DBT still have poor prognosis. Mammography screening may may be more sensitive (i.e., detect more cancers) and have also lead to overdiagnosis. That is, some breast tumors or

20 Breast Cancer Facts & Figures 2019-2020 American Cancer Society Guideline for Table 5. Mammography (%), Women 45 and Older, Breast Cancer Screening, 2015174 US, 2018 Within the The recommendations below are for women at Up to date* past 2 years average risk of breast cancer (i.e., women without (≥ 45 years) (50-74 years) a personal history of breast cancer, a suspected Overall 63 73 or confirmed pathogenic genetic variation [e.g., Age (years) BRCA1 or BRCA2], a strong family history, or a 45-54 53 – 55-64 73 – history of previous radiotherapy to the chest at 50-64 – 72 a young age). All women should become familiar 65-74 75 75 with the potential benefits, limitations, and harms 75+ 51 – associated with breast cancer screening. Race/Ethnicity Non-Hispanic White 64 73 • Women should have the opportunity to begin Non-Hispanic Black 66 74 annual screening between the ages of 40 and 44. Non-Hispanic Asian American 55 71 Non-Hispanic American Indian and 64 66 Alaska Native • Women ages 45 to 54 should be screened annually. Hispanic 60 71 Sexual orientation • Women ages 55 and older should transition Gay/ 70 79 to biennial screening or have the opportunity Straight 63 73 Bisexual † † to continue screening annually. Education Less than high school 52 63 • Women should continue screening mammography High school diploma or GED 61 69 as long as their overall health is good and they Some college/associates degree 64 72 have a life expectancy of 10 years or more. College graduate 70 81 Health insurance status (age ≤64 years) Uninsured 30 39 Insured 64 75 lower recall rates than 2D mammography alone;183, 184 Immigration Born in US 64 73 however, when 2D images are produced separately from Born in US territory 68 † DBT, women receive about twice the dose of radiation. In US fewer than 10 years 43 54 The FDA has approved the use of tomographic images to In US 10 or more years 61 74 GED = General Educational Development high school equivalency. *According produce synthetic 2D images, which reduces the radiation to American Cancer Society recommendations: mammogram within the past dose levels similar to conventional digital mammography, year (ages 45-54 years) or past two years (ages ≥55 years). †Estimate not provided due to instability. Note: Estimates are age adjusted to the 2000 US although this practice is not yet widespread. DBT is not standard population. Mammography prevalence estimates do not distinguish between examinations for screening and diagnosis. yet available in all communities and may not be fully Source: National Health Interview Survey, 2018. covered by health insurance. ©2019, American Cancer Society, Surveillance Research

Prevalence of mammography • Only 30% of uninsured women were up to date with • In 2018, the prevalence of up-to-date mammography breast cancer screening in 2018, compared to 64% of according to American Cancer Society recommendations insured women. was lower among Hispanic and Asian (55%-60%) • The prevalence of up-to-date breast cancer screening women than NH black (66%), NH white, and AIAN was 70% or higher among lesbian women, college (both 64%) women (Table 5).185 However, studies graduates, and those ages 55-74 years. have documented that self-reported survey data overestimate mammography screening prevalence, • In 2016, by state, the prevalence of up-to-date particularly among black and Hispanic women.34- 36, 186 mammography among women ages 45 and older ranged from 57% in Wyoming to 79% in Rhode Island (Table 6).187

Breast Cancer Facts & Figures 2019-2020 21 Table 6. Mammography (%) by State, Women 45 Magnetic resonance imaging (MRI) and Older, 2016 Breast MRI uses high-powered magnets along with radio Within the waves and computers to produce an image. In 2007, the Up to date* past 2 years (≥ 45 years) (50-74 years) American Cancer Society published recommendations Alabama 72 78 for the use of MRI for screening women at increased risk Alaska 58 68 of breast cancer.188 Arizona 66 76 Arkansas 65 73 California 71 82 Beginning at age 30, annual screening with MRI, in Colorado 64 74 Connecticut 77 86 addition to mammography, is recommended for women Delaware 76 82 with an estimated lifetime risk of breast cancer of at least District of Columbia 72 84 Florida 75 82 20%-25% due to the presence of a high-risk variation in Georgia 72 79 the breast cancer susceptibility genes BRCA1 or BRCA2, a Hawaii 74 84 Idaho 58 64 first-degree relative with a BRCA1 or BRCA2 mutation (if Illinois 69 78 the woman herself has not been tested), a strong family Indiana 64 72 history of breast and/or ovarian cancer, prior chest Iowa 71 78 Kansas 68 75 radiation therapy (e.g., for Hodgkin lymphoma), as well as Kentucky 71 77 women with Li-Fraumeni, Cowden, and Bannayan-Riley- Louisiana 70 78 188 Maine 73 81 Ruvalcaba syndromes and their first-degree relatives. Maryland 74 81 Massachusetts 78 86 Michigan 71 79 Women with an estimated 15%-20% lifetime risk, including Minnesota 73 82 women with dense breast tissue, should talk with their Mississippi 65 72 Missouri 69 76 doctors about the benefits and limitations of adding MRI Montana 66 74 screening to their annual mammogram. MRI screening is Nebraska 64 73 not recommended for women whose lifetime risk of breast Nevada 62 73 New Hampshire 73 82 cancer is less than 15%. Studies indicate that MRI is New Jersey 73 81 underutilized among high-risk women and overutilized by New Mexico 60 72 189 New York 70 80 women who are not at high risk for breast cancer. MRI North Carolina 72 79 should supplement not replace mammography and should North Dakota 69 75 Ohio 70 77 be done at facilities that are accredited by the American Oklahoma 66 74 College of Radiology. Although MRI is more expensive Oregon 66 74 than mammography, most major insurance companies Pennsylvania 68 76 Rhode Island 79 85 will cover some portion of the cost if a woman is South Carolina 68 76 demonstrated to be at sufficiently high risk. South Dakota 72 79 Tennessee 68 77 Texas 64 73 Utah 65 77 Vermont 70 79 Virginia 73 80 Breast ultrasound is sometimes used to evaluate Washington 66 76 abnormal findings from a mammogram or physical West Virginia 71 78 Wisconsin 72 80 exam. It is completed with a wand-like handheld device Wyoming 57 64 that captures images of the breast with sound waves. United States (median) 70 78 For women with mammographically dense breast tissue, *According to American Cancer Society recommendations: mammogram within the past year (ages 45-54 years) or past two years (ages ≥55 years). ultrasound combined with mammography may be more Note: Mammography prevalence estimates do not distinguish between examinations for screening and diagnosis. sensitive than mammography alone; however, it also Source: Behavioral Risk Factor Surveillance System, 2016. increases the likelihood of false-positive results.190, 191 ©2019, American Cancer Society, Surveillance Research The use of ultrasound instead of mammograms for breast cancer screening is not recommended.

22 Breast Cancer Facts & Figures 2019-2020 Clinical breast examination (CBE) Breast self-awareness The American Cancer Society no longer recommends Although the American Cancer Society also no longer CBE for breast cancer screening in average-risk recommends that women perform monthly breast asymptomatic women based on lack of clear benefits self-exams (BSE), all women should become familiar with for CBE alone or in conjunction with mammography.174 both the appearance and feel of their breasts and report Furthermore, there is some evidence that adding CBE any changes promptly to their physician. If a lump or to mammography screening increases the rate of false other symptoms develop, women should contact a doctor positives. immediately, even after a recent normal mammogram.

Breast Cancer Treatment

Treatment decisions are made jointly by the patient Surgery and the physician after consideration of the stage and The primary goals of breast cancer surgery are to remove biological characteristics of the cancer, the patient’s age, the cancer and determine its stage. Surgical treatment menopausal status, and preferences, and the risks and involves mastectomy (surgical removal of the entire breast) benefits associated with each option. or breast-conserving surgery (BCS). With BCS (also known as partial mastectomy or ), only cancerous Ductal carcinoma in situ tissue, plus a rim of normal tissue (tumor margin), is removed. BCS is generally not an option in those with high Since there is currently no certain way to determine the tumor-to-breast ratio, multiple tumors within the same progressive potential of a DCIS lesion, surgery and breast, or inflammatory or locally advanced cancers. In sometimes radiation and/or hormonal therapy are the usual most cases, BCS is followed by radiation to the breast. course of action following a diagnosis of DCIS. However, Mastectomy can also be followed by radiation. there is likely a group of patients that could safely forgo 192 surgical treatment for DCIS. Several clinical trials are Despite equivalent survival when combined with radiation, currently underway that are comparing standard treatment BCS-eligible patients are increasingly electing mastectomy to active monitoring (with optional hormonal therapy) in for a variety of reasons, including reluctance to undergo 6 women with “low-risk” DCIS. Ongoing research also seeks radiation therapy, fear of recurrence, and desire for to identify molecular markers of DCIS that could predict symmetry.193, 194 Some women who are diagnosed with recurrence or progression to invasive cancer. breast cancer in one breast also choose to have the unaffected breast removed, which is known as bilateral Invasive breast cancer mastectomy or contralateral prophylactic mastectomy (CPM). Younger patients (<40 years of age) and those with Figure 12 shows treatment patterns among US women larger and/or more aggressive tumors are more likely to with invasive breast cancer in 2016 by stage at diagnosis. be treated with mastectomy or CPM.195-197 Although CPM Most women with early-stage breast cancer will have nearly eliminates the risk of developing a new breast cancer, some type of surgery, which is often combined with other it does not improve long-term breast cancer survival for the treatments such as radiation therapy, chemotherapy, majority of women and nearly doubles the risk of surgical hormone therapy, and/or targeted therapy to reduce the complications.198-200 In the US, the percentage of surgically risk of recurrence. Patients with metastatic disease are treated women with early-stage disease in one breast who primarily treated with systemic therapies, which can undergo CPM has increased rapidly, from 10% in 2004 to include chemotherapy, targeted therapy, hormonal 33% in 2012 among women ages 20-44 and from 4% to 10% therapy, and more recently . among those 45 years of age and older.197

Breast Cancer Facts & Figures 2019-2020 23

Figure 12. Female Breast Cancer Treatment Patterns (%), by Stage, US, 2016 60 56 56

50 49 BCS, no RT BCS RT 40 Mastectomy, no chemo Mastectomy 30 chemo (/- RT) 26 Percent RT and/or chemo No RT, chemo, or 20 18 16 16 treatment-directed surgery 12 12 10 10 6 6 4 4 3 1 1 2 2 0 Stages I and II Stage III Stage IV BCS = breast-conserving surgery; RT = radiation therapy; Chemo = chemotherapy and includes targeted therapy and immunotherapy. Source: National Cancer Data Base, 2016 as provided in C T 21221. ©2019, American Cancer Society, Inc., Surveillance Research

Women who undergo mastectomy may have breast even 20 or more years later.202 Early diagnosis and reconstruction, either with a saline or silicone implant, treatment are critical to reduce the risk of progression tissue from another part of the body, or a combination of to more severe . the two. A woman considering should discuss this option with her breast surgeon prior For more information about breast cancer survivorship, to the mastectomy in order to coordinate the treatment see Cancer Treatment and Survivorship Facts & Figures, plan with a plastic surgeon. available online at cancer.org/statistics.

Both BCS and mastectomy are usually accompanied by Radiation therapy removal of one or a few regional lymph nodes from the Radiation therapy is often used after surgery to destroy armpit (axilla) to determine if the disease has spread cancer cells remaining in the breast, chest wall, or beyond the breast. This procedure identifies the lymph underarm area and reduce the risk of recurrence. BCS is node(s) to which cancer is most likely to spread and is almost always followed by radiation therapy to the breast called sentinel biopsy (SLNB). The presence because it has been shown to reduce the risk of cancer of cancer cells in the lymph nodes increases the risk of recurrence by about 50% at 10 years and the risk of breast recurrence, and so results from the SLNB can help cancer death by almost 20% at 15 years.203 However, determine whether further treatment is needed. Some studies have shown that radiation does not improve breast cancer patients need to undergo more extensive survival for breast cancer patients 70 years of age and lymph node surgery, called an axillary lymph node older with small, lymph node-negative, HR+ cancers who dissection (ALND). Surgery involving the axillary lymph take hormonal therapy, although it does reduce the risk nodes can lead to lymphedema, a serious swelling of the of local recurrence.204 Older patients with HR+ tumors arm caused by retention of lymph fluid. It affects about who opt to omit radiation must be aware of the 20% of women who undergo ALND and 6% of patients heightened importance of adhering to their prescribed who receive SLNB.201 Axillary radiation and excess body hormonal therapy regimen. Some mastectomy-treated weight are also associated with increased risk of patients also benefit from radiation if their tumor is lymphedema. The onset of symptoms usually occurs larger than 5 centimeters, growing into nearby tissues, or within 3 years of surgery, but has been reported to occur

24 Breast Cancer Facts & Figures 2019-2020 if cancer is found in the lymph nodes. Radiation can also that may have migrated to other parts of the body. be used to treat the symptoms of advanced breast cancer, Systemic therapy is the main treatment option for women especially when it has spread to the central nervous with . system or . Systemic therapy can affect fertility in premenopausal Radiation therapy may be administered as external beam women, so young breast cancer patients who are radiation, internal radiation therapy (), or interested in future childbearing should consult with a a combination of both. The method depends on the type, reproductive endocrinologist to determine fertility stage, and location of the tumor, as well as patient prevention strategies. In addition, hormonal therapy is characteristics and doctor and patient preferences. not recommended during pregnancy and chemotherapy External beam radiation is the standard type of radiation, can cause premature ovarian failure. whereby radiation from a machine outside the body is focused on the area affected by cancer. Brachytherapy Chemotherapy uses a radioactive source placed in catheters or other The benefit of chemotherapy is dependent on multiple devices that are put into the cavity left after BCS and is factors, including the size of the tumor and the number of sometimes an option for patients with early-stage breast lymph nodes involved, as well as HR and HER2 status. cancers. Accumulating evidence suggests that radiation Triple negative and HER2+ breast cancers tend to be therapy given at higher doses over fewer days (known as more sensitive to chemotherapy than HR+ tumors.206 accelerated partial breast irradiation) may be as effective There are also gene expression panels (such as Oncotype 205 as conventional therapy. Intra-operative radiation DX, PAM 50, and MammaPrint) that can help assess the therapy, in which a single fraction of radiation is given risk of distant recurrence and potentially identify those who into the cavity left by tumor removal during BCS, is also would more likely benefit from adjuvant chemotherapy. sometimes an option. The Oncotype Dx 21-Gene Recurrence Score is used most widely in the United States, but it is only applicable for Systemic therapy patients with early-stage HR+/HER2- breast cancer. A Systemic therapies are drugs that travel through the high recurrence score identifies women who will benefit bloodstream, potentially affecting all parts of the body, from adjuvant chemotherapy (in addition to hormonal and work using different mechanisms. For example, therapy), whereas a low score identifies women who chemotherapy drugs generally attack cells that grow could safely avoid it. Evidence is less clear for patients quickly. Hormonal therapy works by either blocking or with intermediate risk scores, although recent clinical decreasing the level of the body’s natural hormones, which trial results based on 9 years of follow-up suggest that sometimes act to promote cancer growth. Targeted most patients over age 50 with intermediate scores are 207 therapies work by attacking specific proteins on cancer unlikely to benefit from the addition of chemotherapy. cells (or nearby cells) that normally help them grow. Immunotherapy stimulates the patient’s Although most women who are treated with to attack the cancer. chemotherapy receive it after surgery, a recent study documents an increase in the use of neoadjuvant When systemic therapy is given to patients before chemotherapy, particularly among patients with HER2+ 208 surgery, it is called neoadjuvant or preoperative therapy. and triple negative breast cancers. A summary analysis For larger breast tumors, it is often used to shrink the of clinical trials recently concluded that neoadjuvant tumor enough to make surgical removal easier and less chemotherapy is as effective as the same therapy given 209 extensive (such as BCS in women who would otherwise after surgery in terms of survival and distant recurrence. have required mastectomy). Systemic treatment given to However, breast and axillary surgery remains necessary patients after surgery is called and is after neoadjuvant chemotherapy, even when the used to kill any undetected tumor cells (micrometastases) preoperative treatment appears to have completely

Breast Cancer Facts & Figures 2019-2020 25 cleared all clinical evidence of the cancer. Recent clinical Targeted therapy trials have focused on identifying therapies that can Multiple medications are available for the treatment of improve outcomes among neoadjuvantly treated breast the HER2+ subtype, which accounts for about 15% of all cancer patients who have residual disease detected female breast cancers in the US (Figure 1). , during surgery.210, 211 the first approved drug, is a monoclonal that directly targets the HER2 protein. Several newer drugs Hormonal (endocrine) therapy have been developed that target the HER2 protein and Estrogen, a hormone produced by the ovaries in addition can be used in combination with trastuzumab or if to other tissues, promotes the growth of HR+ breast trastuzumab is no longer working. All invasive breast cancers. About 83% of breast cancers are HR+ (Figure 1) cancers should be tested for HER2 to identify women who and can be treated with hormonal therapy to block the would benefit from this therapy. Additional targeted effects of estrogen on the growth of breast cancer cells. therapy drugs, such as CDK4/6, PARP, and PIK3 These drugs are different than menopausal hormone inhibitors, are available for treatment of select patients therapies, which actually increase hormone levels. with advanced disease.

For premenopausal women, tamoxifen for up to 10 years is Immunotherapy standard treatment; however, the combination of ovarian Immunotherapy drugs are an emerging area of breast suppression and either tamoxifen or an aromatase cancer treatment. These drugs stimulate a person’s own inhibitor is recommended for those women with a high immune system to recognize and destroy cancer cells risk of recurrence.212 For postmenopausal women, more effectively. Checkpoint inhibitors are one type of aromatase inhibitors (i.e., , , and immunotherapy drug that has been identified to treat ) are the preferred hormonal treatment. The some breast cancers, particularly the triple negative decision to treat with an beyond 5 subtype. Drugs that target these checkpoints help to years is individualized based on patient factors and the restore the immune response against breast cancer cells. expected benefit from the reduction in risk of subsequent targets the PD-L1 “checkpoint” and can be breast cancers. Studies have found that to used along with the chemotherapy drug nab- in hormonal therapies remains suboptimal, particularly patients with advanced triple negative breast cancer among black women, and may be in part due to out-of- whose tumor makes the PD-L1 protein.215 Research on pocket costs.213, 214 other immunotherapy drugs for metastatic breast cancer treatment is ongoing.

What Is the American Cancer Society Doing about Breast Cancer?

With a dedicated team of volunteers and staff, the even save – lives. From free rides to treatment and other American Cancer Society is leading the fight for a world cancer-related appointments, places to stay when without breast cancer – and all cancers. treatment is far from home and our 24/7 helpline, we’re here for everyone with cancer questions and concerns, when and where they need us. Patient and services The American Cancer Society provides patients and with resources that can help improve – and

26 Breast Cancer Facts & Figures 2019-2020 Cancer information funded by the Centers for Disease Control and Prevention, we created the Cancer Survivorship Caring, trained American Cancer Society staff connect E-Learning Series for Primary Care Providers. The free people to answers about a breast cancer diagnosis, health e-learning program is designed to teach clinicians how to insurance assistance, American Cancer Society programs care for survivors of adult-onset cancers. and services, and referrals to other services at our 24/7 helpline at 1-800-227-2345. Our website, cancer.org, offers Support for caregivers: Approximately 7% of the US reliable and accurate breast cancer information and news, population is made up of family caregivers of a loved one including current information on treatments and side with cancer, and we are committed to meeting their effects, and programs and services nearby. We also help information, education, and support needs. people who speak languages other than English or Spanish Approximately 4% of the US population is surviving find the assistance they need at cancer.org/easyreading or cancer, meaning the ratio of family caregivers to cancer cancer.org/cancer-information-in-other-languages. survivors is nearly double, supporting the notion that cancer is not isolated only to the individual diagnosed People can visit cancer.org/breastcancer to find information but rather impacts an entire family unit and network of on every aspect of the breast cancer experience, from close friends. One of the informational tools we offer prevention to survivorship. We also publish a wide variety caregivers is our Caregiver Resource Guide, which can of pamphlets and books that cover a multitude of topics, help them: learn to care for themselves as a caregiver, from patient education, quality-of-life and caregiving better understand what their loved one is going through, issues to healthy living. Visit cancer.org/bookstore for a develop skills for coping and caring, and take steps to complete list of books that are available for order. All of help protect their own health and well-being. our books are also available from all major book retailers such as Amazon and Barnes & Noble. Call 1-800-227-2345 or visit cancer.org for brochures. Help navigating the health care system Learning how to navigate the cancer journey and the health care system can be overwhelming for anyone, but Programs and services it is particularly difficult for those who are medically Survivorship: American Cancer Society survivorship underserved, those who experience language or health work aims to help people living with and beyond cancer literacy barriers, and those with limited resources. The from diagnosis through long-term survivorship to the American Cancer Society Patient Navigator Program end of life. Efforts focus on helping survivors understand reaches those most in need. It has specially trained and access treatment; manage their ongoing physical, patient navigators across the country who can help: find psychosocial, and functional problems; and engage in transportation to treatment and other cancer-related healthy behaviors to optimize their wellness. Our appointments; assist with medical financial issues, posttreatment survivorship care guidelines are designed including insurance navigation; identify community to promote survivor healthiness and quality of life by resources; and provide information on a patient’s cancer facilitating the delivery of high-quality, comprehensive, diagnosis and treatment process. coordinated clinical follow-up care. Our survivorship research efforts focus on understanding the impact of Breast cancer support cancer on multiple facets of survivors’ lives and on developing and testing interventions to help survivors The American Cancer Society Reach To Recovery® program actively engage in their health care and improve their connects trained volunteers with breast cancer patients to health and well-being through and beyond treatment. provide peer-to- on everything from practical Through the National Cancer Survivorship Resource and emotional issues to helping them cope with their Center, a collaboration between the American Cancer disease, treatment, and long-term survivorship issues. Society and the George Washington University Cancer

Breast Cancer Facts & Figures 2019-2020 27 Finding hope and inspiration Support after treatment Women with breast cancer and their loved ones do not The end of breast cancer treatment does not mean the have to face their experience alone. The American Cancer end of a cancer journey. Cancer survivors may experience Society Cancer Survivors Network® provides a safe online long-term or late effects resulting from the disease or its connection where cancer patients and caregivers can treatment. The Life After Treatment: The Next Chapter in find others with similar experiences and interests. At Your Survivorship Journey guide may help cancer csn.cancer.org, members can participate on discussion survivors as they begin the next phase of their journey. boards, join the chat room, and build their own support Visit cancer.org/survivorshipguide to download a free copy network from among other members. Other online of the guide. resources, including Springboard Beyond Cancer and Belong, provide additional support for patients, survivors, The American Cancer Society also has a follow-up care and caregivers and allow them to better communicate to guideline for breast cancer survivors that builds upon receive the help they need during and after cancer. available evidence, surveillance guidelines, and standard clinical practice and is designed to facilitate the provision Transportation to treatment of high-quality, standardized, clinical care by primary care providers.216 The breast cancer guideline addresses Lack of transportation can be one of the biggest the assessment and management of potential long-term roadblocks to treatment. That is why the American and late effects, as well as recommendations for health Cancer Society started the Road To Recovery® program. promotion, surveillance for recurrence, screening for It is at the very heart of our work of removing barriers to second primary cancers, and the coordination of care quality health care by providing patients transportation between specialists and primary care clinicians. to treatment through volunteer drivers, partners, or community organizations. Other transportation programs are also available in certain areas. Research Research is at the heart of the American Cancer Society’s Lodging during treatment mission. We invest more in breast than The American Cancer Society Hope Lodge® program any other cancer type. Our funded research has led to the provides a free home away from home for cancer patients development of potentially lifesaving breast cancer drugs and their caregivers. More than just a roof over their such as tamoxifen and Herceptin, as well as improved heads, it is a nurturing community that helps patients understanding of genes linked to breast cancer. Ongoing access the care they need. Through our Hotel Partners research studies span the cancer continuum from Program, we also partner with local hotels across the prevention and early detection to treatment and beyond. country to provide free or discounted lodging for patients As of August 1, 2019, the American Cancer Society is and their caregivers who are not able to make frequent funding more than $67 million in breast cancer research trips for treatment appointments. through 162 research and training grants.

Hair-loss and mastectomy products Examples of projects in which researchers in the American Cancer Society Extramural Research program are engaged The American Cancer Society “tlc” Tender Loving Care® include: publication offers affordable hair loss and mastectomy products for women coping with cancer, as well as advice • Identifying new targets for treating triple negative on how to use those products. Products include wigs, breast cancers hairpieces, hats, turbans and breast forms, as well as • Understanding the role of the immune system in the mastectomy bras, camisoles, and swimwear. Call 1-800- spread of breast cancer to other parts of the body 850-9445, or visit the “tlc”TM website at tlcdirect.org to order products or catalogs.

28 Breast Cancer Facts & Figures 2019-2020 • Evaluating the effects of a high-protein, low-calorie Following are some of the efforts that ACS CAN has been diet on breast tissue and the risk of breast cancer involved with in the past few years to fight breast cancer – recurrence and all cancers:

• Examining the impact of breast density legislation Improving Access to Affordable Care through Health on women’s breast cancer knowledge and screening Care Reform: The Affordable Care Act (ACA) was signed decisions into law on March 23, 2010, giving cancer patients access to quality, affordable health care. All new health insurance Internally, the American Cancer Society also conducts plans, including those offered through state health epidemiologic studies of breast cancer and performs insurance exchanges, are required to cover preventive surveillance and health services research to understand services rated “A” or “B” by the US Preventive Services the factors that underlie racial and socioeconomic Task Force, including mammography screening, at no disparities in breast cancer screening, incidence, cost to patients. Additionally, the ACA removed cost treatment, survival, and mortality. Using information sharing for any preventive services covered by Medicare. collected from more than 600,000 women in Cancer ACS CAN advocates for clear, comprehensive coverage Prevention Study-II, American Cancer Society of these preventive services, including breast cancer epidemiologists study the influence of many risk factors, screening, and encourages states to broaden access to including alcohol consumption, physical activity, health care coverage for all low-income Americans menopausal hormones, family , obesity, through state programs. smoking, and spontaneous abortion on the risk of death from breast cancer. In order to continue to explore the The National Breast and Cervical Cancer Early effects of changing exposures and to provide greater Detection Program (NBCCEDP): Protecting and opportunity to integrate biological and genetic factors increasing funding for the NBCCEDP is a high priority for into studies of other risk factors, more than 304,000 men ACS CAN at both the state and federal levels. Administered and women were enrolled in the American Cancer by the Centers for Disease Control and Prevention, this Society Study-3 (CPS-3), and nearly all successful program provides community-based breast provided a blood sample at the time of enrollment. When and cervical cancer screenings to low-income, uninsured, female participants are diagnosed with breast cancer, and underinsured women. Women who are uninsured consent is requested to bank tumor tissue specimens to are much less likely to be screened for cervical and breast better understand differences in risk and prognostic cancer than those who are insured. The NBCCEDP factors by molecular subtypes of breast cancer. The blood program helps to decrease this disparity in screening. and tissue specimens together with the questionnaire Unfortunately, only one in 10 eligible women can be data collected from CPS-3 participants will provide served by the program due to lack of federal and state unique opportunities for research in the US. funding. ACS CAN is asking Congress and states to increase funding to ensure that more women have access Advocacy to cancer screening. The American Cancer Society’s nonprofit, nonpartisan Protecting the Breast and Cervical Cancer Prevention advocacy affiliate, the American Cancer Society Cancer and Treatment Act (BCCPTA): In 2000, Congress passed Action NetworkSM (ACS CAN), advocates at the federal, the BCCPTA, ensuring that low-income women diagnosed state, and local levels to increase access to quality breast with cancer through the NBCCEDP were provided a cancer screenings, diagnostic and treatment services, pathway to treatment services through their state and care for all women; to increase government funding Medicaid program. for breast cancer research; and to provide a voice for the concerns of breast cancer patients and survivors.

Breast Cancer Facts & Figures 2019-2020 29 In recent years, a number of states have considered populations. ACS CAN supports the federal Patient proposals to eliminate the treatment program due to Navigation Assistance Act, which would create a misconceptions around coverage needs following coverage solution that incentivizes providers to use implementation of the ACA. Additionally, states have patient navigators in order to improve care coordination considered proposals that could jeopardize access to this for patients. The organization also is working with program through the 1115 demonstration waiver process. Congress and federal agencies to help increase funding for patient navigation programs. Breast Density and Mammography Reporting: Mammography sensitivity is lower for women with Funding for Cancer Research: ACS CAN continues to mammographically dense breasts because dense breast work to increase government funding for cancer research tissue makes it harder for doctors to see cancer on at the National Institutes of Health, including the mammograms. The Food and Drug Administration National Cancer Institute and the National Center on proposed a rule to incorporate breast density reporting Minority Health and Health Disparities. on mammograph reports for the first time. ACS CAN has advocated for several years for a national standard It is important to note that the preceding references to developed through an evidence-based process to inform ACA provisions and other federal laws and guidance women about breast density and risk. reflect current law as of June 1, 2019, and do not take into account potential changes to the ACA or other federal Patient Navigation: Patient navigation can improve laws and guidance subsequently considered by Congress quality of cancer care, particularly in vulnerable and the administration.

Sources of Statistics

General information. Unless otherwise stated, the overall US; 2) calculating the average annual percent statistics and statements in this publication refer to change (AAPC) in cases over this time period; and 3) invasive (not in situ) female breast cancer. using the AAPC to project the number of cases three years ahead. These estimates were also partially adjusted Estimated new breast cancer cases. The overall for expected reporting delays using invasive factors. The estimated number of new invasive breast cancer cases estimated number of DCIS invasive cases by age and diagnosed in the US in 2019 was projected using a overall were calculated as the proportions of cases in spatiotemporal model based on incidence data from 48 each age group in the NAACCR data during 2012-2016 states and the District of Columbia for the years 2001- applied to the overall 2019 DCIS and invasive estimates. 2015 that met the North American Association of Central Cancer Registries’ (NAACCR) data inclusion standards.8 Incidence rates. Incidence rates are defined as the This method considers geographic variations in number of people who are diagnosed with cancer divided sociodemographic and lifestyle factors, medical settings, by the number of people who are at risk for the disease in and cancer screening behaviors as predictors of the population during a given time period. Incidence incidence, and also accounts for expected delays in case rates in this publication are presented per 100,000 people reporting. The number of DCIS cases diagnosed in 2019 per year and are age adjusted to the 2000 US standard were estimated by 1) approximating the actual number of population. Breast cancer incidence rates for the US in cases in the 10 most recent data years (2007-2016) by the most recent time period (2012-2016) were calculated applying annual age-specific incidence rates (based on 48 using data on cancer cases collected by NAACCR.8 When states) to corresponding population estimates for the referenced as such, NAACCR incidence data were made

30 Breast Cancer Facts & Figures 2019-2020 available on the NAACCR website (naaccr.org) and within Survival. Five-year survival statistics are based on cancer the Cancer in North America publications.217, 218 Long- patients diagnosed during 2009-2015; 10-year survival term (1975-2016) incidence trends are based on the rates are based on diagnoses during 2001-2015; and 15-year National Cancer Institute’s Surveillance, Epidemiology, survival rates are based on diagnoses during 1998-2015. and End Results (SEER) 9 registries, which account for All patients were followed through 2016. When referenced about 8% of the US population. Analyses of trends (2001- as such, 5-year survival statistics were originally published 2016) by race/ethnicity are based on NAACCR incidence in SEER Cancer Statistics Review, 1975-2016.20 data and were adjusted for reporting delay using delay factors for the SEER 21 registries. Probability of breast cancer diagnosis or death. Probabilities of developing or dying from breast cancer Breast cancer subtype distribtuion. Using the approach were calculated using DevCan 6.7.7 (Probability of of Anderson et al,219 we imputed missing estrogen Developing Cancer Software), developed by the National receptor (ER), (PR), and human Cancer Institute.220 These probabilities reflect the average epidermal growth factor receptor 2 (HER2) status experience of women in the US who were not previously assuming that status was missing at random, conditional diagnosed with breast cancer and do not take into on year of diagnosis, age, race/ethnicity, and ER/PR/ account individual behaviors and risk factors (e.g., HER2 status. Specifically, two-step imputation was utilization of mammography screening and family performed to obtain imputed HR status based on the history of breast cancer). joint distribution of ER (positive, negative, and missing) and PR (positive, negative, and missing) status. Please see Screening. State-level prevalence estimates of DeSantis et al37 for more information on this method. mammography are based on Behavioral Risk Factor Surveillance System (BRFSS) data.187 The BRFSS is an Estimated breast cancer deaths. The overall estimated ongoing system of surveys conducted by the state health number of breast cancer deaths in the US is calculated by departments in cooperation with the CDC. Data from the fitting the number of breast cancer deaths for 2002-2016 CDC’s National Health Interview Survey were used to to a statistical model that forecasts the number of deaths generate national prevalence estimates of expected to occur in 2019. Data on the number of deaths mammography.185 are obtained from the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention Important note about estimated cases and deaths. (CDC). Age-specific estimates were calculated using the While these estimates provide a reasonably accurate proportions of deaths that occurred in each age group portrayal of the current cancer burden in the absence of during 2013-2017 applied to the overall 2019 estimate. actual data, they should be interpreted with caution because they are model-based projections that may vary Mortality rates. Similar to incidence rates, mortality from year to year for reasons other than changes in rates (or death rates) are defined as the number of people cancer occurrence. In addition, they are not informative who die from cancer divided by the number of people at for tracking cancer trends. Instead, trends in cancer risk in the population during a given time period. Death occurrence should be analyzed using age-adjusted rates were calculated using data on cancer deaths incidence rates reported by population-based cancer compiled by NCHS and population data collected by the registries and mortality rates reported by the NCHS. US Census Bureau. All death rates in this publication were age adjusted to the 2000 US standard population.

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38 Breast Cancer Facts & Figures 2019-2020

Acknowledgments We gratefully acknowledge all cancer registries and their staff for their hard work and diligence in collecting cancer information, without which this report would not exist. We also would like to acknowledge the following individuals for their valuable contributions: Rick Alteri; Cammie Barnes; Stacey Fedewa; Ted Gansler; Mia M Gaudet; Gretchen Gierach; Mamta Kalidas; Joan Kramer; Katie McMahon; Kimberly Miller; Lisa A Newman; Caroline Powers; Cheri Richard; Ann Goding Sauer; Scott Simpson; Robert Smith; Lindsey Torre; and Dana Wagner.

Breast Cancer Facts & Figures is a biennial publication of the American Cancer Society, Atlanta, Georgia.

For more information, contact: Carol DeSantis; Rebecca Siegel; Ahmedin Jemal Surveillance and Health Services Research Program ©2019, American Cancer Society, Inc. No. 861019 Models used for illustrative purposes only.

The American Cancer Society’s mission is to save lives, celebrate lives, and lead the fight for a world without cancer.